Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response | Academic Article individual record

Immunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ, and stimulating dendritic cells activation, which induces the cross-priming of CD8(+) T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU, and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy.

author list (cited authors)
Li, T., Cheng, H., Yuan, H., Xu, Q., Shu, C., Zhang, Y., ... Tan, X.
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  • Apoptosis
  • Interferon Regulatory Factor-3
  • Mice, Inbred BALB C
  • Antineoplastic Agents
  • Animals
  • Nucleotides, Cyclic
  • Cytokines
  • Cell Line, Tumor
  • Immunity, Innate
  • Dendritic Cells
  • Fluorouracil
  • Membrane Proteins
  • Nucleotidyltransferases
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